The Seattle-Lausanne-Kampala Clinical Trials Unit (SLK CTU) shares a common goal over the next seven years to work toward a world free of AIDS. The proposed CTU, administered through Fred Hutchinson Cancer Research Center (FHCRC), will consolidate three current high-performing CTUs and add one new experienced, high-capacity CRS in sub-Saharan Africa. The SLK CTU will harness the collective diverse expertise of six international HIV-1 leaders who have made significant contributions to improve HIV-1 vaccine development, prevention and care over the past 2-3 decades. The four integrated Clinical Research Sites (CRSs) will address four NIAID HIV network leadership agendas: Seattle VMP (vaccine, microbicide, and prevention), UW ACTU in Seattle (adult therapeutic), Lausanne VIC (Centre Hospitaller Universitaire Vaudois) (vaccine), and Kasangati-lnfectious Diseases Institute (IDI) in Kampala (prevention and adult therapeutic). To accomplish the CTU's common goal and the networks' agendas, clinical research studies and activities will be directed toward the following four specific aims: Specific Aim 1: Contribute leadership and expertise to address current and new scientific priorities related to HIV-1 vaccination, prevention, microbicides and therapeutics. Specific Aim 2: Provide centralized administrative oversight through consolidation of the current infrastructure and operations of our existing CTUs and clinical trials programs, to integrate and expand the CRS activities within the four networks. Specific Aim 3: Conduct phase 1-3 clinical trials under the direction of the four NIAID- sponsored HIV networks and provide the trial support necessary to ensure the highest quality standards of clinical research. Specific Aim 4: Continue and extend partnerships with the CRS communities and stakeholders to enlist their support and guarantee successful enrollment and participation of relevant study populations that are impacted by the HIV epidemic. Our CTU recognizes the challenges moving forward. Inherent characteristics of our structure, expertise, and ability to leverage related activities in our rich environment offer innovation to the clinical trials networks.